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PathY5 > Haemotology of Systemic Disease > Flashcards

Haemotology of Systemic Disease Flashcards

1
Q

What could a patient with lymphoma presenting with jaundice, anaemia and raised LDH be due to?

A

Lymphoma stage 4 with bone marrow +liver involved

Lymphoma with nodes compressing the bile duct plus anaemia of inflammation

Lymphoma with Acquired auto immune haemolytic anaemia

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2
Q

What is something that may be the first presentation of cancer?

A

Anaemia

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3
Q

What kind of anaemias are associated with cancer?

A

Iron deficiency
Anaemia of inflammation (ACD)
Leucoerythroblastic anaemia
Haemolytic anaemia

+Secondary polycythaemia (e.g. renal cell cancer/ liver)

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4
Q

Why may iron deficiency anaemia occur in cancer?

A

Occult blood loss:

  • GI cancers (Gastric/ colon)
  • Urinary tract cancers (renal cell carcinoma/ bladder cancer)
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5
Q

What are the biochemical findings in IDA?

A

Reduced ferritin, transferrin sat

Raised TIBC (total iron binding capacity)

Bleeding until proven otherwise

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6
Q

What are 2 unusual cancer blood syndromes?

A

Leucoerythroblastic anaemia

Acquired haemolytic anaemia
Immune mediated

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7
Q

What is acquired haemolytic anaemia?

A

Immune mediated
Non Immune; fragmentation (micro-angiopathic haemolytic anaemia)

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8
Q

Why is the first finding of cancer Leucoerythroblastic anaemia and Acquired haemolytic anaemia?

A

Often associated with an underlying cancer or systemic disease. Because of the frequency of FBC testing it may be the first laboratory abnormality detected.

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9
Q

What is leucoerythroblastic anaemia?

A

Red and white cell precursor anaemia

with variable degrees of anaemia

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10
Q

What are the blood film features of leucoerythroblastic anaemia?

A

Teardrop RBCs (+aniso and poikilocytosis)

Nucleated RBCs

Immature myeloid cells

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11
Q

What are the causes of leucoerythroblastic anaemia?

A

Cancer (Haematopoeitic/ Non haematopoeitic)

Severe infection (Miliary Tb, severe fungal infection - uncommon)

Myelofibrosis (Massive splenomegaly, Dry tap on BM aspirate)

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12
Q

What haematopoeitic and non haematopoietic cancers can cause leucoerythroblastic anaemia?

A

Haematopoeitic: Leukaemia/ lymphoma/ myeloma

Non- haematopoietic:
Breast, bronchus, prostate

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13
Q

What are the distinguishing features of haemolysis on FBC?

A

Anaemia (but may be compensated)
Reticulocytosis
Raised BR (unconjugated)
Raised LDH
Reduced haptoglobins

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14
Q

What are the two groups of haemolytic anaemia?

A

Inherited: Defects of the red cell
Acquired: Defects of the environment in which the Red cell finds herself

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15
Q

What qualities would you expect in inherited anaemia?

A
  • Lab features present
  • Ethnic bg
  • FH/ PMH
  • Pigment gallstones
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16
Q

What are the 3 components of a red cell?

A

Membrane
Haemoglobin
Enzymes

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17
Q

Which blood malformations affect membrane?

A

Spherocytosis
Elliptocytosis

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18
Q

Which diseases have haemoglobin malformations?

A

Sickle cell disease (structural)
Thalassaemia (Quantitative)

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19
Q

What is an enzyme based blood disorder?

A

G6PD

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20
Q

What are the two types of acquired haemolytic anaemia?

A

Immune
Non immune

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21
Q

How do you distinguish between immune and non immune acquired haemolytic anaemias?

A

DAT/ Coombs

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22
Q

What will be found if an autoimmune anaemia is present?

A

Spherocytes
DAT positive

+/- associated system disorder e.g. lymphoma, SLE, infection due to immune disturbance, AI disease, idiopathic

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23
Q

What is seen on a blood test for immune haemolytic anaemia?

A

Reticulocytosis
Raised BR (unc)
Raised LDH

+DAT (idiopathic or underlying AI disease/ lymphocytic blood cancer)

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24
Q

What is acquired immune haemolytic anaemia linked to?

A

Infection (malaria)

Micro-angiopathic Haemolytic anaemia (MAHA)

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25
Q

What are signs of MAHA?

A

Red cell fragments (microangiopathy)

Low PLT

DIC (fibrin deposition/ degradation)/ bleeding

may be linked to underlying adenocarcinoma

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26
Q

What causes true polycythaemia?

A

Polycythaemia vera (PV) - clonal myeloproliferative disorder (JAK2 mutation)

Secondary Polycythaemia (Raised EPO)

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27
Q

What are the causes of secondary polycythaemia?

A

Cancer: HCC, bronchial and renal cancer

Oxygen related: High altitude, hypoxic lung disease, cyanotic heart disease

28
Q

How can white cells change in systemic disease?

A

Increase/ decreased
Mature or immature
Cell type
Lineages (red, white, platelets)

29
Q

What systemic diseases may change white cells?

A

Inflammatory
> Auto immune
> Infective

Malignant

Genetic

Metabolic

30
Q

What are the normal types of white cells?

A

Granulocytes
Monocytes
T lymphocytes
B lymphocytes
NK cells

31
Q

What are the immature white cells?

A

Blasts
Promyelocytes
Myelocytes

32
Q

How do you investigate WCC?

A

FBC/ blood film

HIgh WBC/ look at lineage/ morphology/ maturity

33
Q

What causes neutrophilia?

A

corticosteroids

underlying neoplasia

tissue inflammation (e.g.colitis, pancreatitis)

Pyogenic infection

myeloproliferative/ leukaemic disorders
infection

34
Q

Which infections cause neutrophilia?

A

Localised and systemic infections
acute bacterial, fungal, certain viral infections

Some infections characteristically do not produce a neutrophilia e.g. brucella, typhoid, many viral infections.

35
Q

What is reactive neutrophilia?

A

Presence bands, toxic granulation, and signs of infection/inflammation

36
Q

What is malignant neutrophilia?

A

Neutrophilia basophilia plus immature cells myelocytes, and splenomegaly. Suggest a myeloproliferative (CML)
Neutropenia plus Myeloblasts (AML)

37
Q

When does reactive eosinophilia occur?

A

Parasitic infestation

allergic diseases e.g. asthma, rheumatoid, polyarteritis,pulmonary eosinophilia.

Underlying Neoplasms, esp. Hodgkin’s, T-cell NHL (reactive eosinophilia)

Drugs (reaction erythema mutiforme)

38
Q

Why does chronic eosinophilic leukaemia occur?

A

Eosinophils part of the “clone”

FIP1L1-PDGFRa Fusion gene

39
Q

When does monocytosis occur?

A

Rare but seen in certain chronic infections and primary haematological disorders
TB, brucella, typhoid
Viral; CMV, varicella zoster
sarcoidosis
chronic myelomonocytic leukaemia (MDS)

40
Q

Summarise the infections where there is elevated levels of each phagocyte

A

Neutrophils: bacterial
Eosinophils: Parasitic
Basophils: Pox viruses
Monocytes: Chronic (TB/ brucella)

41
Q

Which inflammatory diseases have raised Neutrophils or Eosinophils?

A

N: AI disease, Tissue necrosis
E: Allergic (Asthma, atopy, drug)

42
Q

Which phagocytes are linked to neoplasia?

A

Neutrophils: all types

Eosinophils: Hodgkins/ NHL

43
Q

Which phagocytes cause myeloproliferative disorders?

A

Neut: CML
Baso: CML
Monocytes: CMML

44
Q

Which phagocytes cause myeloproliferative disorders?

A

Neut: CML
Baso: CML
Monocytes: CMML

45
Q

How do you tell if something is secondary or primary?

A

Secondary (reactive); polyclonal response to infection, chronic inflammation

Primary; monoclonal lymphoid proliferation e.g. CLL, NHL. Is it T or B cell?

46
Q

How do you interpret a lymphocytosis?

A

Approach

Clinical
Symptoms suggestive of infection or lymphoma
Massive lymphadenopathy or splenomegaly

FBC
Degree of lymphocytosis

Light microscopy/ morphology
Mature cells or primitive lymphoblasts

Flow cytometry
Lineage; B or T cells
Stage of differentiation

Molecular genetics
Rearranged: T cell receptor or Immunoglobulin gene

47
Q

What causes reactive lymphocytosis?

A
  1. Infection (EBV, CMV, Toxoplasma, viral hepatitis, rubella, herpes infections)
  2. Autoimmune disorders
  3. Sarcoidosis
48
Q

How do you interpret morphology in lymphocytosis?

A

Mature lymphocytes (PB)
reactive/atypical lymphocytes (IM)
small lymphocytes and smear cells (CLL/NHL)

Immature Lymphoid cells in PB
lymphoblasts (Acute Lymphoblastic Leukaemia)

49
Q

What is lymphocytosis?

A

>3.5x109/l

50
Q

How does flow cytometry work?

A

Monoclonal antibody conjugated to fluorescent dye
Anti-CD4/blue, CD34/green, CD7/purple

51
Q

What info can you get from a flow cytometer?

A

Forward scatter: Size
Side scatter: granularity

52
Q

Is CD2 expressed on normal T cells?

A

Yes

53
Q

What are some primary germline disorders of Factor IX and Erythrocytes?

A

Germline/inherited (gene mutated):
Factor IX
▪ Deficiency > haemophilia B
▪ Excess > FIX Padua (gene therapy)

Erythrocytes
▪ Deficiency> b globin chain production > b Thalassaemia
▪ excess > VHL gene > Chuvash polycythaemia

54
Q

What are some secondary disorders of erythrocyte and Factor VIII excess and deficiency?

A

Erythrocytes
◼ Excess > hypoxia > cyanotic heart disease
◼ Deficiency> anti-RBC antibodies > Immune haemolysis

Factor VIII
◼ Excess > inflammatory response
◼ Deficiency>anti-FVIII auto-antibodies (acquired
haemophilia A)

55
Q

what are the names of the conditions when there is raised or reduced: soluble factors, erythrocytes, platelets, leucocytes?

A

Soluble factors:
◼ raised FVIII in Inflammation > Thrombosis risk.

Erythrocytes
◼ Raised {altitude/hypoxia or Epo secreting tumour}
◼ Reduced
BM infiltration or deficiency disease {Vit B12 or Fe}
Shortened survival {Haemolytic anaemia}

Platelets
◼ Raised {Bleeding, Inflammation, splenectomy}
◼ Reduced
BM infiltration or deficiency disease {Vit B12 }
Shortened survival {ITP, TTP}

Leucocytes
◼ Raised {Infection, Inflammation, corticosteroids}
◼ Reduced
BM infiltration or deficiency disease {Vit B12 }

56
Q

What are some primary acquired haematological diseases of Erythrocytes and Myelocytes?

A

Somatic/acquired (gene mutated) BM rapid turnover organ!

Erythrocytes
▪ Excess> JAK2 V617F> Polycythaemia vera

Myeloid/granulocytes
▪ BCR-ABL1 > Chroinic myeloid leukaemia

57
Q

What is the difference in ratio of light chains between reactive and malignant b cells?

A

60: 40 kappa and lambda
99: 1 kappa or lambda skewed

58
Q

What investigations can you do in haematology?

A

>Morphology- blood film/ biopsy- architecture of tumour, cytology, cytochemistry

>Immunophenotype- flow cytometry, immunohistochemistry

>Cytogenetics- conventional karyotyping, fluorescent in-situ hybridisation (FISH), Interphase FISH, Metaphase FISH

>Molecular genetics- mutation detection, direct sequencing, Pyrosequencing, PCR analysis, gene expression profiling, whole genome sequencing

59
Q

How do you classify the malignant cell and link it to it’s normal cell counterpart?

A

Primitive lymphoid blast cells expressing B cell marker > B cell Acute lymphoid leukaemia

Mature lymphoid cells expressing T cell antigens and involving skin> cutaneous T cell lymphoma

Mature erythrocytes with JAK2 mutation> polycythaemia vera

60
Q

What are 2 disorders of soluble protein deficiency?

A

◼ Factor VIII > Haemophilia A> bleeding
◼ Protein C > pro-thrombotic

61
Q

What are the disorders of red cell quantity?

A

Polycythaemia
Anaemia

62
Q

What are examples of excesses of granulocytes and lymphocytes?

A

Granulocytes > leukaemia(CML) or reactive eosinophilia

Lymphocytes > leukaemia(CLL) or Lymphopenia (HIV)

63
Q

What is a disorder of platelets?

A

Essential thrombocythemia or ITP

64
Q

What are primary disorders?

A

Primary disorders arise from DNA mutation(s)

65
Q

What is a secondary disorder?

A

Secondary disorders are changes in haematological
parameters 2ndry to a non-haematological disease

PathY5 (98 decks)

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